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Detection/measurement of malaria infection disease utilizing natural immunity by hemozoin induction, screening of preventative or therapeutic medicine for malaria infection disease, and regulation of natural immunity induction

a malaria infection and natural immunity technology, applied in the field of detection/measurement of malaria infection disease utilizing natural immunity by hemozoin induction, screening of preventative or therapeutic medicine for malaria infection disease, and regulation of natural immunity induction, can solve the problems of human disease and mortality

Active Publication Date: 2012-05-24
OSAKA UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The present invention is about detecting and measuring malaria infection using a method that involves detecting and measuring the immune response induced by hemozoin, a hydrophobic heme polymer produced by malaria parasites. The invention provides a method for diagnosis, screening of vaccines and preventative or therapeutic agents, as well as an adjuvant for regulating innate immunity. The invention also relates to the use of hemozoin as an immunostimulant for inducing TLR9-mediated, MyD88-dependent innate immunity. The technical effects of the invention include improved diagnosis and treatment of malaria infection, as well as the development of a novel adjuvant for regulating innate immunity.

Problems solved by technology

Malaria infection is the major cause of disease and mortality of humans, especially in the tropical regions of the world.

Method used

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  • Detection/measurement of malaria infection disease utilizing natural immunity by hemozoin induction, screening of preventative or therapeutic medicine for malaria infection disease, and regulation of natural immunity induction
  • Detection/measurement of malaria infection disease utilizing natural immunity by hemozoin induction, screening of preventative or therapeutic medicine for malaria infection disease, and regulation of natural immunity induction
  • Detection/measurement of malaria infection disease utilizing natural immunity by hemozoin induction, screening of preventative or therapeutic medicine for malaria infection disease, and regulation of natural immunity induction

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Effect test

example 1

Activation of Innate Immune Activity by HZ and the Regulation Thereof

(Materials and Methods)

(Mice)

[0043]Mutant mice (MyD88-, TRIF-, TLR2-, TLR4-, TLR7-, and TLR9-deficient mice) either on a 129 / Ola×C57 / BL6 or C57 / BL6 background were generated as described in literatures (Immunity 9: 143-150, 1999; Immunity 11: 443-451, 1999; Nature 408: 740-745, 2000; Nat. Immunol. 3: 196-200, 2002; Science 301: 640-643, 2003). Age-matched groups of wild type mice and mutant mice were used for experiments. For in-vivo studies, 1500 μg HZ purified from P. falciparum culture and synthetic HZ (β-hematin) were injected intraperitoneally into wild-type mice, MyD88− / − mice, or TLR9− / − mice (J. Immunol. 172: 3101-3110, 2004). Sera were collected from tails at 1, 2, 4, and 6 hours for cytokine ELISA.

(Reagents)

[0044]Synthetic CpG oligodeoxynucleotides (ODN) D35 were synthesized and purchased from Hokkaido System Science Co., Ltd. Lipopolysaccharides (LPS) from Salmonella minnesota Re-595, hemin chloride, and...

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Abstract

The instant invention is to provide a method for detecting and measuring malaria infection utilizing the induction by hemozoin (HZ); a method for screening a vaccine for malaria infection and a preventative or therapeutic agent for malaria infection using the method for detecting and measuring; and a means for regulating the induction of innate immunity using the HZ, synthetic HZ, or derivatives thereof as an adjuvant or immunostimulant. Malaria infection is detected and measured of by detecting and measuring HZ-induced, TLR9-mediated, and MyD88-dependent innate immune activity. The detection and measurement of malaria infection can be used to diagnose malaria infection. The method for detecting and measuring is also used for screening a vaccine for malaria infection and a preventative or therapeutic agent for malaria infection. Further, HZ, synthetic HZ, or derivatives thereof are used as an adjuvant or immunostimulant to regulate HZ-induced innate immune induction.

Description

CROSS-REFERENCE TO RELATED PATENT APPLICATIONS[0001]This application is a Divisional of U.S. application Ser. No. 11 / 792,668, which is the US National Stage application of PCT / JP2005 / 020283, filed Nov. 4, 2005, which claims priority from Japanese application JP 2004-357255, filed Dec. 9, 2004, the entire contents of which are incorporated by reference herein.[0002]The instant application contains a Sequence Listing which has been submitted in ASCII format via EFS-WEB and is hereby incorporated by reference in its entirety. Said ASCII copy, created on Dec. 5, 2011, is named sequence.txt and is 14 KB.BACKGROUND OF THE INVENTION[0003]1. Technical Field[0004]The instant invention relates to a method for detecting and measuring malaria infection by detecting and measuring TLR9-mediated, MyD88-dependent innate immune activity induced by hemozoin, hydrophobic heme polymers produced as a hemoglobin metabolite by malaria parasites; screening of a vaccine for malaria infection or a preventati...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K31/555C12N5/071A61K38/02
CPCA01K2267/0387G01N2500/10G01N2333/445G01N33/56905A61P31/00A61P33/06Y02A50/30A61K39/015A61K2039/572G01N2333/70596
Inventor AKIRA, SHIZUOISHIICOBAN, CEVAYIR
Owner OSAKA UNIV
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